Saccharides are ubiquitously present in plants and some are quite inexpensive. Even highly purified sucrose can be obtained at low cost. All of the hydroxyl groups of a saccharide molecule can be chemically modified, e.g., the eight hydroxyl groups of sucrose. The degree of modification can be controlled, for instance, by changing the reaction ratio. These considerations have led to extensive research on the chemistry of the saccharides, particularly the least expensive ones.
For example, the research literature reveals that sucrose has been used to build polymer networks [Gruber, H. (1981); Patil, D., et al., (1991); Garcia-Gonzalez, et al., (1993)]. Glycidyl (meth)acrylates have been used to modify polysaccharides, such as starch [Lepisto, M., et al. (1983); Laakso, T., et al., (1987); Artursson, P., et al. (1984)] and dextran [Edman, P., et al. (1980); Smedt, S. C. D., et al. (1995)]. Also, the formation of swellable hydrogels from proteins, such as albumin, has been described [Park, K., (1988); Shalaby, W. S. W., et al. (1990)]. Polymer hydrogels and microspheres have been made by these approaches.
Hydrophilic gels have been prepared from sucrose, for example, by polymerization of a sucrose ester. Thus, polymerization of a sucrose acrylate monomer has been described [Strumia, M. C., et al. (1991)]. Further, linear polyesters of sucrose have been described [Patil et al., (1991)]. These latter sucrose linear polyesters were produced using an enzyme system.
Although extensive research has been performed on hydrogels, little research is related to hydrogel foams. When the hydrogel foams are formed, the polymer chains are separated by empty spaces. Thus, water can be absorbed into the foams by capillary reaction. Furthermore, the porous structure affords foams having hundreds of times more surface area and shorter diffusion distance than hydrogels, making the swelling rate of foams hundreds of times faster than that of hydrogels. The fast swelling ability is important, for instance, in designing controlled release drug delivery systems, especially oral dosage forms [Shalaby, W. S. W., et al. (1992)].
Additionally, environment-sensitive hydrogels have been studied extensively. Hydrogels having the ability to respond to changes in environmental factors such as pH, temperature, electric field, or light can find application in drug delivery, biotechnology, biosensors, and semiconductors. Moreover, hydrogels that can respond to stimuli caused by particular diseases may provide a basis for developing new smart drug delivery systems. For example, attempts have been made to develop hydrogel systems that respond to pH changes and specific ligands in delivering insulin, however, they are unsatisfactory. [Jeong, S. Y., et al., (1984); Horbett, T. A., et al. (1984)].
Thermoreversible hydrogels have been proposed for use in a new drug delivery system as well as a bioseparation system [Yoshida, R., et al., (1993); Hoffman, A. S., et al., (1986); Dong, L. C., et al., (1986)]. Various applications for thermoreversible hydrogel systems have been proposed by researchers [Shalaby, S. W. (1991)].
Thermoreversible hydrogels prepared by the copolymerization of N-isopropyl acrylamide and methacrylic acid, lightly crosslinked with N,N-methylene-bisacrylamide have been studied [Hoffman, A. S., et al., (1986); Dong, L. C., et al., (1986)]. Copolymer hydrogels of N-isopropyl acrylamide and butyl methacrylate reportedly exhibited thermoreversible changes in volume with temperature [Bae, Y. H., et al., (1988)]. Also, hydrogels containing N-methacryloyl .alpha.-amino acid esters and 2-hydroxypropyl methacrylate, which were crosslinked with polyethylene glycol (600) dimethacrylate, were reported to show temperature-dependent reversible volume changes [Yoshida, M., et al., (1989)]. Hydrogels synthesized from methacryloyl dipeptides have also been characterized [Yoshida, M., et al., (1991)]. In addition, an interpenetrating polymer network of N-acryloyl pyrrolidone and poly(oxyethylene) has been described [Bae, Y. H., et al. (1987)].
In the patent art, U.S. Pat. No. 3,103,508 discloses polymerizable esters formed from sugars and .alpha.,.beta.-unsaturated polymerizable acids.
U.S. Pat. No. 3,215,137 discloses an immobilizing bandage which employs a sucrose ester, the viscosity of which may be reduced by addition of a polyethylene glycol dimethacrylate.
U.S. Pat. No. 3,225,012 discloses nylon-type polyamides derived from carbohydrates.
U.S. Pat. No. 3,356,652 discloses vinyl derivatives of tetra-acetylated glucose.
U.S. Pat. No. 4,042,538 discloses vinylbenzoyl esters of mono- and disaccharides, which can be copolymerized with styrene or methacrylates.
U.S. Pat. No. 4,663,388 discloses a "coupling agent", which comprises a saccharide having a pendant ethylenically unsaturated group, such as an acrylamide moiety.
U.S. Pat. No. 5,164,492 relates to approaches to forming polymers having saccharide residues at their sidechains.
U.S. Pat. No. 5,116,961 discloses the formation of a trimethacryloyl sucrose having methylated hydroxyl groups. U.S. Pat. No. 5,248,747, which is a continuation-in-part of U.S. Pat. No. 5,116,961, relates to polymers formed using the trimethacryloyl sucrose as a cross-linking agent.
Desired are novel saccharide monomers that can be polymerized to form biodegradable gels and foams. Such gels and foams should be more environmentally friendly than purely synthetic gels and foams, and may be imparted with physical and chemical properties conducive to their use in medical and veterinary applications.